Nitric oxide antioxidant role

As mentioned earlier, ascorbate and ubihydroquinone regenerate a-tocopherol contained in a LDL particle and by this may enhance its antioxidant activity. Stocker and his coworkers [123] suggest that this role of ubihydroquinone is especially important. However, it is questionable because ubihydroquinone content in LDL is very small and only 50% to 60% of LDL particles contain a molecule of ubihydroquinone. Moreover, there is another apparently much more effective co-antioxidant of a-tocopherol in LDL particles, namely, nitric oxide [125], It has been already mentioned that nitric oxide exhibits both antioxidant and prooxidant effects depending on the 02 /NO ratio [42]. It is important that NO concentrates up to 25-fold in lipid membranes and LDL compartments due to the high lipid partition coefficient, charge neutrality, and small molecular radius [126,127]. Because of this, the value of 02 /N0 ratio should be very small, and the antioxidant effect of NO must exceed the prooxidant effect of peroxynitrite. As the rate constants for the recombination reaction of NO with peroxyl radicals are close to diffusion limit (about 109 1 mol 1 s 1 [125]), NO will inhibit both Reactions (7) and (8) and by that spare a-tocopherol in LDL oxidation. 

Belkner et al. [32] demonstrated that 15-LOX oxidized preferably LDL cholesterol esters. Even in the presence of free linoleic acid, cholesteryl linoleate continued to be a major LOX substrate. It was also found that the depletion of LDL from a-tocopherol has not prevented the LDL oxidation. This is of a special interest in connection with the role of a-tocopherol in LDL oxidation. As the majority of cholesteryl esters is normally buried in the core of a lipoprotein particle and cannot be directly oxidized by LOX, it has been suggested that LDL oxidation might be initiated by a-tocopheryl radical formed during the oxidation of a-tocopherol [33,34]. Correspondingly, it was concluded that the oxidation of LDL by soybean and recombinant human 15-LOXs may occur by two pathways (a) LDL-free fatty acids are oxidized enzymatically with the formation of a-tocopheryl radical, and (b) the a-tocopheryl-mediated oxidation of cholesteryl esters occurs via a nonenzymatic way. Pro and con proofs related to the prooxidant role of a-tocopherol were considered in Chapter 25 in connection with the study of nonenzymatic lipid oxidation and in Chapter 29 dedicated to antioxidants. It should be stressed that comparison of the possible effects of a-tocopherol and nitric oxide on LDL oxidation does not support importance of a-tocopherol prooxidant activity. It should be mentioned that the above data describing the activity of cholesteryl esters in LDL oxidation are in contradiction with some earlier results. Thus in 1988, Sparrow et al. [35] suggested that the 15-LOX-catalyzed oxidation of LDL is accelerated in the presence of phospholipase A2, i.e., the hydrolysis of cholesterol esters is an important step in LDL oxidation. 

The administration of Qio or quercetin to rats protected against endotoxin-induced shock in rat brain [252]. It was found that the pretreatment with these antioxidants diminished the shock-induced increase in brain MDA and nitric oxide levels. Interesting data have been obtained by Yamamura et al. [253] who showed that ubiquinone Qi0 is able to play a double role in mitochondria. It was found that on the one hand, Q10 enhanced the release of hydrogen peroxide from antimycin A- or calcium-treated mitochondria, but on the other hand, it inhibited mitochondrial lipid peroxidation. It was proposed that Q10 acts as a prooxidant participating in redox signaling and as an antioxidant suppressing permeability transition and cytochrome c release. 

Kang KW, Choi SH, Kim SG. 2002. Peroxynitrite activates NF-E2-related factor 2/ antioxidant response element through the pathway of phosphatidylinositol 3-kinase The role of nitric oxide synthase in rat glutathione S-transferase A2 induction. Nitric Oxide 7 244-253. 

Mann GE, Rowlands DJ, Li FY, de Winter P, Siow RC. 2007. Activation of endothelial nitric oxide synthase by dietary isoflavones Role of NO in Nrf2-mediated antioxidant gene expression. Cardiovasc Res 75 261-274. 

Laroux FS, Lefer DJ, Kawachi S, Scalia R, Cockrell AS, Gray L, Van der Heyde H, Hoffrnan JM and Grisham MB, Role of nitric oxide in the regulation of acute and chronic inflammation. Antioxid Redox Signal 2(3) 391-6,2000. 

The initial chapters introduce to the general knowledge necessary to understand flie inflammatory process and the role played of free radical and oxidative stress. The interplay between inflammatory molecules and cell signalling is also dealt with in depth. A second part is dedicated to nitric oxide, redox regulation and antioxidant function in inflammation. The final chapters are devoted to diseases where inflammation plays the dominant role septic shock, end-stage renal disease, neurodegenerative, ischemic and lung diseases. 

Oxidative stress is suggested to play a major role in the pathogenesis of AD. Vitamin C has been regarded as the most important antioxidant in neural tissue. Vitamin C decreases p-amyloid generation and acetylcholinesterase activity and prevents endothelial dysfunction by regulating nitric oxide. Clinical trials with different antioxidants, including vitamin C, yielded confusing results [485],... 

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